When Drosophila and other insects are challenged by microbial infections, they mount a complicated immune response generally divided into the humoral and cellular responses. Recent evidence suggests that one or more rel signal transduction systems participate in regulating these immune responses. Our long term objectives include understanding the molecular roles of proteins that comprise these signaling systems. A maternally-encoded signal transduction pathway whose function is crucial in establishment of the dorsal-ventral polarity of the Drosophila embryo is well characterized. This pathway involves functions of the rel protein dorsal, its cytoplasmic inhibitor cactus and the transmembrane receptor Toll. New evidence suggests that dorsal, cactus and Toll also have zygotic functions and may be involved in regulating the immune response during larval stages. The understanding of their functions in the maternal signal transduction pathway provides a paradigm for the functions of dorsal, cactus and Toll proteins in the immune response. The specific goals of this study are: (1) To clarify the specific roles of dorsal, cactus, Toll and other known rel proteins suspected to function in the immune response: multiple experimental approaches are described. (2) To isolate and characterize new components involved in both the cellular and humoral immune responses: molecular and genetic techniques are suggested. (3) To understand the nature of interactions between humoral and cell-mediated immune responses: transformation experiments are suggested. (4) To understand the functions of the fat body and hemocytes in the immune response in vivo. ;